Solute Carrier Family 26

The SLC26 gene family encodes multifunctional anion exchangers and anion channels that transport a wide range of substrates. The mammalian SLC26 gene family has 11 members, SLC26A1-SLC26A11. The SLC26 polypeptides are characterized by N-terminal cytoplasmic domains, 10-14 hydrophobic transmembrane spans, and C-terminal cytoplasmic STAS domains, and appear to be homo-oligomeric. SLC26-related SulP proteins of marine bacteria likely transport HCO₃^- as part of oceanic carbon fixation. SulP genes present in antibiotic operons may provide sulfate for antibiotic biosynthetic pathways. The SLC26-associated Sultr proteins transport sulfate in unicellular eukaryotes and plants. The STAS domains are required for cell surface expression of the SLC26 proteins and contribute to the regulation of cystic fibrosis transmembrane regulator in complex, cell- and tissue-specific ways. The protein interactomes of SLC26 polypeptides are under active investigation. Some SLC26 family members show highly specific tissue expression patterns, others are widely expressed.

Fig.1 Structural topology model of SLC26 polypeptides showing the short cytoplasmic N-terminal region followed by a transmembrane domain with 12 putative membrane-spanning α-helices, and the C-terminal cytoplasmic region, largely comprising the STAS domain. (Alper, 2013)

Three rare recessive diseases in humans, namely diastrophic dysplasia (cartilage disorder resulting in growth retardation), congenital chloride diarrhoea (anion exchange disorder of the intestine) and Pendred syndrome (deafness with thyroid disorder) turned out to be caused by the highly related genes SLC26A2, SLC26A3, and SLC26A4, respectively. Additional disease phenotypes evident only in mouse knockout models include oxalate urolithiasis for SLC26A6 and SLC26A1, non-syndromic deafness for SLC26A5, gastric hypochlorhydria for SLC26A7 and SLC26A9, distal renal tubular acidosis for SLC26A7, and male infertility for SLC26A8.

Human SLC26 Family Members
SLC26A1	SLC26A2	SLC26A3	SLC26A4	SLC26A5
SLC26A6	SLC26A7	SLC26A8	SLC26A9	SLC26A11

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Reference

Alper S L and Sharma A K. (2013). The SLC26 gene family of anion transporters and channels. Mol Aspects Med. 34(2-3): 494-515.

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